Nontypable Haemophilus influenzae (NTHi) is one of the major etiological agents of acute otitis media (AOM) which has very high morbidity among children in both developing and developed countries. The long term goal of this research is to better understand NTHi pathogenesis and human immune responses following nasopharyngeal (NP) colonization and AOM, in order to develop strategies for intervention in the disease. We will prospectively collect NP, middle ear fluids (MEF), and sera from young children age 2 to 24 months, who are otitis prone, have infrequent otitis, or remain otitis free. We propose to evaluate the role of specific immune responses to NTHi outer membrane proteins P2, P5, P6, and OMP26 in clearance of NP colonization by comparing children who clear colonization with those who experience prolonged colonization. In addition, we will establish a repository of prospectively collected mucosal and serum samples for other researchers in otitis media. The specific aims of this research are: Specific Aim 1: To prospectively collect NP secretions, MEF, and sera from young children who are otitis prone, have infrequent otitis, or remain otitis free. Specific Aim 2: To evaluate the role of specific immune responses to NTHi P2, P5, P6, and OMP26 in clearance of AOM by comparing children with different AOM experiences and in clearance of NP colonization by comparing children with different colonization experiences. Specific Aim 3: To establish a repository of prospectively collected mucosal and serum samples for future research in otitis media. Relevance to Public Health: This project is specifically responsive to research needs identified at an NIAID and NIDCD-organized workshop held at the NIH on 8-9 June 2004 on "Vaccines for Otitis Media: Proposals for Overcoming Obstacles to Progress." The results gained from these studies will provide insight to the immune mechanisms involved in the pathogenesis of otitis media aid in the development of a vaccine for otits media.